Amalyte has in-licensed a small molecule anti-inflammatory NCE with Phase II clinical data in allergic rhinitis (AR). The Company is developing the compound under the drug code name AM3301 for multiple clinical indications in gastrointestinal (GI) inflammatory (IBD and IBS) and in allergic (rhinitis and asthma) diseases. For allergic rhinitis, clinical activity has already been demonstrated, along with an impressive array of biochemical, cellular and animal pharmacology studies. Animal studies also have shown AM3301 to be as active as 5-ASA and CysA in TNBS-induced colitis and as active as sulfasalazine and prednisolone in DSS-induced colitis in rats. In addition, the compound has a remarkably clean preclinical safety package and an established, economical manufacturing process.
AM3301, displays a unique and highly selective pharmacological profile in a battery of both in vitro and in vivo experiments, inhibiting both IgE-mediated mediator release from mast cells (histamine, leukotrienes “LT”, PGD2) and cytokine production (particularly IL-4 and IL-5) from eosinophils and other inflammatory cells. The pharmacological results are comparable to control anti-histamine, LT receptor antagonists and prednisone in the relevant models. Since most experts consider allergic rhinitis and asthma multi-factorial diseases, requiring blockade of both early and late phases of the allergic response to achieve a therapeutic effect, the compound might be considered the ideal drug to address these diseases.
While there are several research issues being addressed, Amalyte’s approach is to quickly validate, in parallel, the potential efficacy of AM3301 in both ulcerative colitis and allergic rhinitis. In the case of GI indications, the current formulation of AM3301 is being used to establish human proof-of- concept in a Phase IIa ulcerative colitis trial. For allergic indications, a new oral formulation for AM3301 with improved pharmacokinetic and pharmacologic properties will be developed prior to additional clinical research. In addition to the above clinical development and formulation activities, a series of molecular and cellular studies will be initiated to further characterize the mechanism of action for AM3301.
Market Opportunities
Gastrointestinal Disease
The worldwide market for prescription IBD products is $1.7B, of which 70% ($1.2B) is in the US. The U.S. and E.U. prevalence of Crohn’s disease is estimated to be approximately 800K in 2007 and is forecast to grow at 0.6% p.a. to almost 900K by 2018. The U.S. and E.U. prevalence of ulcerative colitis disease is estimated to be approximately 770K in 2007 and is forecast to grow at 0.5% p.a. to approximately 800K by 2018. In the U.S. and E.U., treatment for IBD is symptomatic, with the use of biologics increasing and surgery decreasing. Key therapies include anti-rheumatic agents, immunosuppressants, and intestinal and anti-inflammatory agents. There are 13 products in or past Phase III trials, and 42 products in Phase II trials. The major unmet need for treatment of IBD is fewer side-effects, followed by simpler administration and lower expense, and then more efficacious.
Allergic Rhinitis
The market for allergic rhinitis prescription drugs is currently between $3-4 billion annually and it is rapidly growing. Fourteen percent of the adult population suffers from allergic rhinitis (45 MM patients in the US) and many have significant co-morbidities, including sinusitis, asthma, migraine and depression. The AR market is growing rapidly with >10% growth over each of the last three decades. There are a wide variety of medications used, with 53% of patients using OTC products. Consequently, allergic rhinitis is associated with the largest disease burden of any major chronic respiratory disease by virtue of its high prevalence and its impacts on quality of life and productivity.
Not only is AR a very large market, but it is highly unsatisfied as well. First, there is the reluctance associated with chronic use of steroids, one of the only effective treatments for nasal congestion. Also, the disease has a major impact on patients’ daily lives with over 40% of adults reporting sleep disturbances and a third reporting effects on school/work performance. Moreover, in children and adolescents the figures reach 80-95%. Even those taking prescription medications are highly unsatisfied based on key findings from recent patient surveys.
Due to AM3301’s potential efficacy profile and because it is not a steroid, Amalyte believes that AM3301 has the potential to address many of the limitations of the three classes of marketed prescription drugs available for allergic rhinitis – oral anti-histamines, oral LT receptor antagonists and topical (intranasal) steroids. Based on a wealth of preclinical data and the initial Phase IIa data, AM3301 potentially has the same profile as an intranasal steroid. As a novel “non-steroidal” therapy with the potential to be formulated both orally and topically to address ease-of-use issues, Amalyte believes AM3301 would have a major impact both in the clinic and in the marketplace.